Plotting a career change
08 May 2009 (Volume 4 Issue 7)
Cells normally responsible for keeping the immune response in check can transform into stimulators of immune activity if placed in the proper environment
Figure 1: An image of a germinal center in a Peyer’s patch, showing fluorescently tagged cells Foxp3+ T cells (green), TFH cells derived from Foxp3+ T cells (blue), and activated B cells (red) capable of producing IgA.
enlarge imageMany animals benefit from the presence and support of a diverse community of microorganisms within their gut. However, it is also important that these bacteria be kept in their place, and prevented from invading the intestinal lining and thereby causing harm to their host.
Research by Sidonia Fagarasan and colleagues at the RIKEN Research Center for Allergy and Immunology (RCAI) in Yokohama has revealed that maintenance of this ecosystem depends on production of immunoglobulin A (IgA) within clumps of immune cells known as Peyer’s patches. IgA is generated specifically by B cells within sites known as germinal centers (GCs), a process that also requires participation of specialized T cells known as TFH cells. However, the nature and origin of these TFH cells has remained enigmatic. Fagarasan says that she and her team realized that very little is actually known about the T cells that are involved in this process.
Fortunately, an ongoing collaboration between her laboratory and that of RCAI colleague Shohei Hori has proven fruitful in illuminating this mystery1. Since T cell-deficient mice fail to develop functional GCs, the researchers began by investigating whether transplantation of different T cell types restores their formation. Hori’s group is particularly interested in regulatory T cells (Treg), which inhibit the immune system to prevent it from ‘overreacting’ or triggering an autoimmune response. Hori’s team has demonstrated that these cells are characterized by strong expression of the Foxp3 gene, which encodes a protein essential to their development and function, but also found that some Treg cells show greatly reduced Foxp3 expression and capacity for immune suppression when introduced into T cell-deficient mice. When Hori and Fagarasan examined the Peyer’s patches of these mice, they found—surprisingly—that many of these cells had adopted the characteristics of TFH cells.
Most importantly, transplantation of these cells was sufficient to drive proper GC formation and activation of IgA-producing B cells (Fig. 1). “It was most surprising to us that these T cells, considered ‘professional suppressor cells’, were the most efficient helpers of immune responses in the gut,” says Hori. “Our findings thus require immunologists to reconsider the concept of Treg cells.”
This unexpected capacity for immune cell adaptation raises many questions, and Hori and Fagarasan are looking to dissect the mechanism underlying this Treg-to-TFH transition. “The final goal is to understand how the immune system converts and adapts its cells to be able to maintain the homeostasis—especially the delicate balance of the intestine,” says Fagarasan.
The corresponding author for this highlight is based at the Research Center for Allergy and Immunology
- Tsuji, M., Komatsu, N., Kawamoto, S., Suzuki, K., Kanagawa, O., Honjo, T., Hori, S. & Fagarasan, S. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer’s patches. Science 323, 1488–1492 (2009). | article |
The corresponding authors for this highlight are based at the RIKEN Research Unit for Immune Homeostasis and the RIKEN Laboratory for Mucosal Immunity
